Purpose: Systemic chemotherapy regimens with cisplatinum have been associated with several toxicities. Thus, a loco-regional therapy approach may greatly reduce the toxicity. For this purpose, we designed this experimental study to investigate whether local chemotherapeutic injection is superior to systemic cisplatinum injection for retroperitoneal lymph nodes. Methods: A total of 48 male Wistar rats were included to the study. Rats were divided into six groups. In the first three groups, systemic applications of cisplatinum, carbo-platinum and oxaliplatin were performed, respectively. In the last three, local administration of cisplatinum, carbo-platinum and oxaliplatin was performed, respectively. One hour after the chemotherapeutic agent applications, retro-peritoneal lymph nodes were dissected and platinum concentrations were analyzed. Results: When compared with systemic route, achieving higher platinum concentrations in the local chemothera-peutic application groups was the most spectacular result of the study. Serum platinum concentrations were also lower in the local application groups than systemic ones. When we compared local and systemic applications between three chemotherapeutic agents, the most significant concentration difference was seen in carboplatinum group. Conclusion: The results of this study demonstrate that intralymphatic delivery of cisplatinum, carboplatinum and oxaliplatin leads to higher drug concentrations in the retroperitoneal lymph nodes when compared with intravenous administration. © Springer-Verlag 2012.